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Baicalin Prevents Colon Cancer by Suppressing CDKN2A Protein Expression
Gang-Gang Li1, Xiu-Feng Chu1, Ya-Min Xing1
1Henan Key Laboratory of Helicobacter pylori, Microbiota and Gastrointestinal Cancers, Marshall Medical Research Center, Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, 400015, China.
Objective:
To observe the therapeutic effects and underlying mechanism of baicalin against colon cancer.
Methods:
The effects of baicalin on the proliferation and growth of colon cancer cells MC38 and CT26. WT were observed and predicted potential molecular targets of baicalin for colon cancer therapy were studied by network pharmacology. Furthermore, molecular docking and drug affinity responsive target stability (DARTS) analysis were performed to confirm the interaction between potential targets and baicalin. Finally, the mechanisms predicted by in silico analyses were experimentally verified in-vitro and in-vivo.
Results:
Baicalin significantly inhibited proliferation, invasion, migration, and induced apoptosis in MC38 and CT26 cells (all P<0.01). Additionally, baicalin caused cell cycle arrest at the S phase, while the G0/G1 phase was detected in the tiny portion of the cells. Subsequent network pharmacology analysis identified 6 therapeutic targets associated with baicalin, which potentially affect various pathways including 39 biological processes and 99 signaling pathways. In addition, molecular docking and DARTS predicted the potential binding of baicalin with cyclin dependent kinase inhibitor 2A (CDKN2A), protein kinase B (AKT), caspase 3, and mitogen-activated protein kinase (MAPK). In vitro, the expressions of CDKN2A, MAPK, and p-AKT were suppressed by baicalin in MC38 and CT26 cells. In vivo, baicalin significantly reduced the tumor size and weight (all P<0.01) in the colon cancer mouse model via inactivating p-AKT, CDKN2A, cyclin dependent kinase 4, cyclin dependent kinase 2, interleukin-1, tumor necrosis factor α, and activating caspase 3 and mouse double minute 2 homolog signaling (all P<0.05).
Conclusion:
Baicalin suppressed the CDKN2A protein level to prevent colon cancer and could be used as a therapeutic target for colon cancer.
Insights
Baicalin effectively inhibits colon cancer growth by inducing apoptosis and cell cycle arrest. This natural compound targets key proteins like CDKN2A, offering a potential new therapeutic strategy for colon cancer treatment.
Area of Science:
- Pharmacology and Molecular Biology
- Oncology Research
- Natural Product Therapeutics
Background:
- Colon cancer remains a significant global health challenge, necessitating novel therapeutic strategies.
- Baicalin, a flavonoid derived from Scutellaria baicalensis, has demonstrated potential anti-cancer properties.
- Understanding the precise molecular mechanisms of baicalin in colon cancer is crucial for its clinical application.
Purpose of the Study:
- To elucidate the therapeutic effects of baicalin on colon cancer.
- To identify and validate the molecular targets and pathways affected by baicalin in colon cancer.
Main Methods:
- In vitro studies assessed baicalin's impact on colon cancer cell proliferation, migration, invasion, and apoptosis.
- Network pharmacology, molecular docking, and Drug Affinity Responsive Target Stability (DARTS) were employed to predict and confirm molecular targets.
- In vitro and in vivo experiments validated the predicted mechanisms in colon cancer models.
Main Results:
- Baicalin significantly inhibited colon cancer cell proliferation, invasion, and migration while inducing apoptosis and S-phase cell cycle arrest.
- Network pharmacology identified 6 key therapeutic targets, with molecular docking and DARTS confirming baicalin's interaction with CDKN2A, AKT, caspase 3, and MAPK.
- In vivo studies demonstrated that baicalin reduced tumor size and weight by modulating key signaling pathways, including inactivating AKT and activating caspase 3.
Conclusions:
- Baicalin exhibits significant therapeutic effects against colon cancer by suppressing proliferation and inducing apoptosis.
- The study identified CDKN2A as a critical target protein suppressed by baicalin, contributing to its anti-cancer activity.
- Baicalin presents a promising candidate for colon cancer therapy, with CDKN2A serving as a potential therapeutic target.
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